Long-term survival and cause-specific mortality after event-free survival at 24 months (EFS24) in mantle cell lymphoma: an international multicohort study

The prognostic significance of event-free survival at 24 months (EFS24) in mantle cell lymphoma (MCL) has not been fully defined in the era of contemporary immunochemotherapy. We analyzed 3179 patients from five cohorts (Mayo Clinic/Iowa MER, US 12-center, BC Cancer, Swedish, and Danish) diagnosed between 2002 and 2020. Two treatment eras were defined per cohort based on shifts in frontline immunochemotherapy. In the MER cohort, patients achieving EFS24 in the earlier era had inferior OS compared with age- and sex-matched general population (standardized mortality ratio [SMR] = 2.36, 95% CI 1.74–3.14), whereas survival approached expected OS in the contemporary era (SMR = 1.38, 95% CI 0.90–2.02). After EFS24, lymphoma remained the leading cause of death in the earlier era (5-year lymphoma vs non-lymphoma mortality 18% vs 8%) but not in the contemporary era (8% vs 9%). Similar trends were observed in other cohorts. Post-EFS24 survival approached that of the general population in the US 12-center cohort (SMR = 1.44) in the contemporary era, and improved from earlier to contemporary eras in BC Cancer (SMR 4.99 vs 3.56), Swedish (SMR 4.26 vs 3.17), and Danish (SMR 2.36 vs 2.23) cohorts. In the contemporary era, 5-year lymphoma-related mortality was comparable to or lower than other mortality: 12% vs 12% in BC Cancer, 6% vs 9% in US 12-center, and 13% vs 18% in Swedish cohorts. These findings demonstrate that achieving EFS24 in MCL is associated with improved conditional survival approaching general population expectations and declining lymphoma-related mortality in the era of contemporary immunochemotherapy.